tbuckley/cabot-search huggingface dataset:
OP0272 EARLY RESPONSE IN RHEUMATOID FACTOR LEVELS PREDICTS SUBSEQUENT CLINICAL RESPONSE TO DISEASE MODIFYING TREATMENT OF RHEUMATOID ARTHRITIS
Authors: V. Konzett, D. Aletaha
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid factors (RF) are well established prognostic biomarkers in rheumatoid arthritis (RA), but the clinical relevance of their dynamics is not yet well understood. Here, we evaluate the implications of changes in RF levels in RA patients with newly initiated disease modifying (DMARD) treatment. <h3>Objectives</h3> To analyze how early responses of RF levels relate to subsequent disease activity outcomes in RF positive RA patients initiating DMARD treatment. <h3>Methods</h3> We analyzed data from 1999 RA outpatients, starting either a conventional (csDMARD) or biologic/targeted synthetic DMARD (btsDMARD). RF response to treatment was defined as a ≥50% reduction in RF levels or complete seroconversion to RF negativity. We investigated the prognostic implication of early RF response on the timing of achieving disease control as defined by Simplified Disease Activity Index (SDAI) low disease activity (LDA) or remission (REM) in patients with SDAI moderate or high disease activity (MDA/HDA) at baseline. We analyzed the first two years of each treatment segment; patients, who did not reach LDA/REM within two years, or patients who switched therapy within this time frame were censored in this Kaplan Meier analysis. In a Cox proportional hazard model we adjusted the observed effects for gender, age and disease duration, as well as for SDAI at month 3. <h3>Results</h3> RF response (as defined above) to treatment was observed in 11%, 25.5% and 41% of RF positive RA patients at 3, 6 and 12 months after treatment initiation, respectively; RF response was seen in comparable frequency in csDMARD and btsDMARD treated patients (Table 1). LDA or REM by SDAI in patients with MDA or HDA was achieved significantly earlier in RF responders as compared to non-responders (Wilcoxon p=0.042 for csDMARDs, p=0.005 for btsDMARDs). Crude effects of RF response on achieving LDA/REM were highly significant in the Kaplan Meier analysis (p&lt;0.0001; Figure 1) and remained so after adjusting for multiple variables including disease activity levels at 3 months (p&lt;0.0001); in a pooled analysis of all DMARD starts (N = 736), the adjusted Hazard Ratio (HR) for LDA or REM in the RF response group was 1.73 (95% confidence interval: 1.23 to 2.42), compared to the RF non-responders. <h3>Conclusion</h3> Change in RF levels or complete seroconversion at the 3-month timepoint predict the achievement and timing of treatment goals within a 6 to 24-month period after treatment initiation. This finding was independent of disease activity improvement at 3 months, and may therefore serve as an additional early biomarker in assessing a patient's future chance of achieving treatment targets in RA. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0326 POLYGENIC RISK SCORE OF RHEUMATOID ARTHRITIS PREDICTS BONY EROSION
Authors: T. S. Wu, Y. J. Chen, W. N. Huang, Y. H. Chen, Y. M. Chen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Polygenic risk scores (PRS) are widely used to estimate disease risks and predict clinical outcomes. However, differences exist among PRS derived from genome-wide association study (GWAS) of ethnicities across the globe. <h3>Objectives</h3> We aimed to build up PRS for predicting the development of rheumatoid arthritis (RA) in a Taiwanese population and investigate whether PRS of RA may be associated with bone erosion. <h3>Methods</h3> We constructed PRS using GWAS data from a hospital-based cohort of 2044 RA cases and 7950 non-RA controls participating in the Taiwan Precision Medicine Initiative. LDpred2, PLINK and PRsice2 models were used to evaluate the area under curve (AUC) of RA susceptibility in both training and testing datasets (1022 RA cases and 3975 controls). Demographic data, seropositivity of rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), treatment with biological and targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs and tsDMARDs) and bone erosions by either plain x ray or ultrasonography were compared among quantiles of PRS. <h3>Results</h3> PRS of 97,396 single nucleotide polymorphisms derived from LDpred2 exhibited the highest AUC for predicting the development of RA in the overall dataset as compared with the remaining algorithms. Participants with the top RA-PRS quantile have the highest proportion of RF and ACPA positivity (74.8% &amp; 65.0%, respectively), bone erosion (86.4%) and higher chance to receive bDMARDs or tsDMARDs (42.3%) as compared to the counterparts. In addition, RA-PRS quantile was a significant risk for bone erosion in the multivariate regression model with the adjustment of RF, ACPA positivity and therapeutic medication, specifically in the group of age &lt; 60 years. <h3>Conclusion</h3> PRS is associated with seropositivity, erosive bone disease, need for advanced therapy in Taiwanese patients with RA. <h3>Reference</h3> [1]Honda S, Ikari K, Yano K, Terao C, Tanaka E, Harigai M, Kochi Y. Association of Polygenic Risk Scores With Radiographic Progression in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2022 May;74(5):791-800. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0185 SYSTEMIC IMMUNE-INFLAMMATION INDEX TO ALL-CAUSE MORTALITY IN GOUT PATIENTS: NHANES 2007-2018
Authors: H. Lin, N. Chen, S. X. Hu, Q. H. LI
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic immune inflammatory index (SII) is a new marker of inflammation. SII is associated with increased cancer risk and mortality in cardiovascular and cancer patients. However, the effect of SII on mortality in gout patients is rarely reported in the literature. <h3>Objectives</h3> To study the relationship between SII level and all-cause mortality in gout patients. <h3>Methods</h3> This prospective cohort study included participants 20 years or older with gout enrolled from the 2007-2008 through 2017-2018 annual NHANES cycles. The data of mortality and its underlying causes to 31 December 2019 were obtained from the National Death Index records. The SII level was calculated as the platelet counts × neutrophil counts/lymphocyte counts. Gout patients were grouped according to low, middle and high tertile of SII. Generalize linear regression was used to study variables influencing SII. The relationship between SII level and mortality were analyzed by Cox proportional hazards analysis. <h3>Results</h3> A total of 1334 gout patients were included with median follow-up time 68 months (34 months, 106 months). As shown in the Table 1, gout patients with high SII level were characterized by more having chronic kidney diseases, diabetes mellitus and less fiber intake (P &lt;0.05). The generalized linear model found that SII level was positively correlated with diabetes mellitus (P&lt;0.05), and negatively correlated with men, eGFR, fiber intake (P&lt;0.05). Kaplan Meier survival curve showed that mortality was highest in the high SII group (Figure 1). Cox proportional hazards analysis after multivariable adjustment showed that taking low SII group as the reference group, mortality was elevated in the high SII groups (Table 1). <h3>Conclusion</h3> High SII is a predictor of all-cause death in gout patients. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0136 PERFORMANCE OF THE AMERICAN COLLEGE OF RHEUMATOLOGY-1997, THE SYSTEMIC LUPUS INTERNATIONAL COLLABORATING CLINICS-2012, AND THE EUROPEAN LEAGUE AGAINST RHEUMATISM-2019 CRITERIA FOR CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A SOUTHEAST ASIA VALIDATION STUDY
Authors: K. L. Teh, Y. X. Book, S. F. Hoh, X. Gao, L. Das, T. Arkachaisri
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Classification criteria for systemic lupus erythematosus (SLE) include the American College of Rheumatology (ACR) 1997, the Systemic Lupus International Collaborating Clinics (SLICC) and the European League Against Rheumatism (EULAR)/ACR criteria<sup>[1]</sup>. Their performance in a primarily Asian childhood-onset SLE (cSLE) population remains unclear as the clinical manifestation frequencies are different<sup>[2]</sup>. <h3>Objectives</h3> To evaluate the diagnostic performance of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria in a cSLE cohort in Singapore. <h3>Methods</h3> Cases were physician-diagnosed cSLE, while controls were children with mixed and undifferentiated connective tissue disease that posed an initial diagnostic challenge. Retrospective data were reviewed to establish the three criteria fulfilled at diagnosis and over time. <h3>Results</h3> The study population included 120 cSLE cases and 36 controls, Table 1. Among cSLE patients, low C3/4 (94.2%), immunologic (93.3%), hematologic manifestations (90.0%) and arthritis (60.8%) were the most common over time. At diagnosis, 102 (85%) patients fulfilled all criteria, Figure 1. SLICC-2012 had the highest sensitivity (97.5%) and negative predictive value (NPV, 89.3%), while ACR-1997 had the highest specificity (91.7%) and positive predictive value (PPV, 97.2%). All criteria had diagnostic accuracies of ≥ 85%. Over time, 113 (94.2%) fulfilled all criteria. SLICC-2012 remained the criteria with highest sensitivity (99.2%) and NPV (94.7%), while ACR-1997 remained the criteria with highest specificity (75.0%) and PPV (92.7%). Only SLICC-2012 and ACR-1997 had ≥ 85% diagnostic accuracy over time. <h3>Conclusion</h3> This is the first study evaluating the SLE classification criteria performance in Southeast Asian cSLE cohort. SLICC-2012 criterion has the highest sensitivity and diagnostic accuracy, with acceptable specificity in our cohort, especially early in the disease course. The EULAR/ACR-2019 criteria does not confer additional benefits compared to the earlier two criteria. <h3>References</h3> [1]Chang, L. S., Huang, P. Y., Kuo, H. C., Tu, Y. K., Tseng, P. T., Liang, C. S., &amp; Hsu, C. W. (2022). Diagnostic accuracy of the American College of Rheumatology-1997, the systemic lupus international collaborating clinics-2012, and the European league against Rheumatism-2019 criteria for juvenile systemic lupus erythematosus: A systematic review and network meta-analysis. Autoimmunity Reviews, 103144. [2]Tang, S. P., Lim, S. C., &amp; Arkachaisri, T. (2021). Childhood-onset systemic lupus erythematosus: Southeast Asian perspectives. Journal of Clinical Medicine, 10(4), 559. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0190 INFLUENCE OF AGE, PERIOD, AND BIRTH COHORT EFFECTS ON SECULAR TREND IN GOUT INCIDENCE IN THE UNITED KINGDOM
Authors: J. Ye, Y. Zhang, W. Zhang, M. Doherty, N. Lu, C. Zeng, G. Lei, J. Wei
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The risk of incident gout in the United Kingdom (UK) appears to have declined since 2013.<sup>[1]</sup> However, whether this is temporary or likely to continue is unclear. <h3>Objectives</h3> To examine the influence of age, calendar year, and year of birth on recent gout incidence in the UK. <h3>Methods</h3> Using data from IQVIA Medical Research Database in the UK, we identified incident gout by READ codes from 1999 to 2019. We grouped age, calendar year, and year of birth into 3-year categories. We assessed the effect of age, calendar year, and birth cohort categories on the incidence rate of gout using the age-period-cohort model among all participants and in men and women separately. <h3>Results</h3> Over the 21 years, there were 164,588 incident gout cases. The incidence rate of gout increased with age until age 80, then leveled off (P for trend &lt;0.001) (Figure 1A). The gout incidence increased from 1999 to 2013, then declined (Figure 1B). The incidence rate of gout was higher in the late birth cohorts than in the early birth cohorts from the Year 1999 to the Year 2013 (Figure 1C); however, such a trend was reversed after the Year 2013, with the incidence rate of gout being higher in the early birth cohorts than that in the late birth cohorts (Figure 1D). Similar patterns were observed in men and women. <h3>Conclusion</h3> Using the age-period-cohort model, we found that the risk of gout in the UK increased from 1999 to 2013 and then declined afterward. These findings suggest that some environmental factors occurring after 2013 may play role. Such a downward trend of the risk of gout may continue if these environmental factors are still present. <h3>Reference</h3> [1]Abhishek A, Tata LJ, Mamas M, et al. Has the gout epidemic peaked in the UK? A nationwide cohort study using data from the Clinical Practice Research Datalink, from 1997 to across the COVID-19 pandemic in 2021. Ann Rheum Dis 2022 Jan 27. <h3>Acknowledgements</h3> This work was supported by the National Natural Science Foundation of China (81930071, 82072502, U21A20352), Project Program of National Clinical Research Center for Geriatric Disorders (2021LNJJ06, 2022LNJJ07), the Natural Science Foundation of Hunan Province (2022JJ20100), and the Science and Technology Innovation Program of Hunan Province (2022RC3075, 2022RC1009). <h3>Disclosure of Interests</h3> None Declared.
POS0189 COMPARATIVE RISK OF RETINAL VASCULAR COMPLICATIONS IN PATIENTS WITH GOUT INITIATING FEBUXOSTAT VERSUS ALLOPURINOL: A POPULATION-BASED COHORT STUDY
Authors: M. J. Kim, A. Shin, S. R. Choi, Y. J. Ha, Y. J. Lee, E. B. Lee, E. H. Kang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Comparative cardiovascular (CV) safety studies on patients with gout have showed in general a similar risk between allopurinol and febuxostat. However, the data have been derived from macrovascular rather than microvascular CV outcomes. <h3>Objectives</h3> In this study, we aimed to compare the risk of retinal vascular complications among patients with gout initiating febuxostat versus allopurinol. <h3>Methods</h3> Using the 2012-2020 Korean National Health Insurance service database, we conducted a population-based cohort study on patients with gout aged ≥40 years initiating febuxostat or allopurinol. After 1:1 propensity score (PS) matching in non-diabetes (non-DM) and DM subgroups, respectively, on &gt;60 covariates, subgroups were merged for a main cohort. The primary outcome was a composite of retinal vascular complications (retinal vascular occlusions, retinal disorders of retinopathy and vascular changes, degeneration, and hemorrhage, and other retinal disorders). DM retinopathy was investigated as a secondary outcome in DM subgroup. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing allopurinol and febuxostat users. Subgroup-specific HRs were pooled by a fixed effect model. <h3>Results</h3> We included 89,642 PS-matched pairs of febuxostat and allopurinol users in non-DM subgroup and 28,734 PS-matched pairs in DM subgroup, with 118,876 pairs in total (mean 57.3 years, 83.7% male). During a mean 223 days of follow-up, 1,318 composite outcomes occurred. The pooled HR [95% CI] for retinal microvascular complications was 0.98 [0.83-1.15] with 0.94 [0.76-1.15] in non-DM and 1.05 [0.80-1.39] in DM subgroup. The HR [95% CI] for DM retinopathy of 0.86 [0.67-1.11]. <h3>Conclusion</h3> In this large cohort study on patients with gout, we found a similar risk of retinal microvascular complications. <h3>Reference</h3> [1]Shin A, Choi SR, Han M, Ha YJ, Lee YJ, Lee EB, Kang EH. Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat. Semin Arthritis Rheum. 2022 Oct;56:152080. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0609 EXPANDED CYTOTOXIC CD8+ T CELL CLONES CHARACTERIZE THE BLOOD OF INCLUSION BODY MYOSITIS PATIENTS
Authors: L. Shakib, M. Fein, A. Bloostein, D. Fernandez, L. Donlin
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Inclusion body myositis (IBM) is an inflammatory myopathy, characterized by CD8+ T cell infiltration of muscle and patients present with progressive muscle weakness and atrophy, leading to disability due to no FDA-approved therapies. Patients with IBM have been noted to frequently exhibit aberrant expansion of circulating CD8+ T cells, even satisfying classification criteria for T cell large granular lymphocytic leukemia (T-LGL) in &gt;50% of cases, in one study<sup>[1]</sup>. However, high-resolution profiling of the transcriptome and TCR repertoire in IBM are lacking. <h3>Objectives</h3> To evaluate the TCR repertoire of circulatory CD8+ T cells, allowing us to simultaneously define the transcriptomes of expanded and non-expanded clonotypes in blood of IBM patients and healthy age-matched blood donors. <h3>Methods</h3> 13 IBM patients and 9 age-matched healthy controls were sorted for either non-naïve CD8+ T cells and/or CD8+CD57+ T cells by flow cytometry. Single-cell RNA and TCR sequencing was performed to profile the whole gene expression, coupled with paired TCRa and TCRb chains, at single-cell resolution. Additional markers during flow cytometry allowed for further identification of aberrant populations in IBM compared to age-matched healthy controls. <h3>Results</h3> Our results found IBM CD8+ T cell were highly expanded compared to age-matched healthy controls. These CD8+ T cells were identified in both the broad non-naïve T cell population, as well as the specific CD8+ CD57+ T cell subset. Enrichment of T-LGL leukemia genes, in addition to CD8+ effector function, cytotoxicity and inflammatory chemokines and cytokines were found in expanded clonotypes, with a higher gene expression found in hyperexpanded clones compared to minimally expanded clonotypes. Absence of common TCR clonotypes between patients in IBM was found, a pattern also seen in T-LGL leukemia. GSEA analysis also confirmed a downregulation of cell apoptosis processes in hyperexpanded clonotypes, a feature of T-LGL leukemia clones. <h3>Conclusion</h3> Significant clonal expansion of CD8+ T cells in the blood was found in our IBM cohort compared to our age-matched healthy controls. Additionally, these hyperexpanded clonotypes have various T-LGL leukemia gene markers, in addition to elevated cytotoxic and T cell activation genes in comparison to their minimally expanded counterparts. These results highlight how the blood compartment of IBM, a progressive muscle disease, is important in IBM and how future studies and therapies should be targeting these aberrant blood CD8+ T cell clones. <h3>Reference</h3> [1]Greenberg SA, Pinkus JL, Amato AA, Kristensen T, Dorfman DM. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia. Brain. 2016 May;139(Pt 5):1348-60. doi: 10.1093/brain/aww024. Epub 2016 Feb 26. PMID: 26920676. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0511 LIFESTYLE MODIFICATION FOR THE PREVENTION OF CARDIOVASCULAR DISEASE IN PATIENTS WITH GOUT
Authors: S. M. Jung, K. J. Kim, J. S. Yun
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> High morbidity and mortality of cardiovascular (CV) disease in patients with gout draw attention to CV risk management in daily clinical practice. <h3>Objectives</h3> To evaluate the effect of a favorable lifestyle on the incident CV events in patients with gout. <h3>Methods</h3> We identified 9,110 patients with gout from UK Biobank Cohort based on the combination of self-report and/or hospital diagnostic codes. Lifestyle behaviors defined by smoking status, physical activity, obesity and diet were categorized into favorable (≥ 3 healthy factors), intermediate (2 healthy factors), and unfavorable patterns (0-1 healthy factor). CV risk was estimated in participants with and without gout according to serum uric acid (SUA) levels and lifestyle patterns. <h3>Results</h3> Incidence rate of CVD was significantly higher in patients with gout than in participants without gout (11.38 vs 5.49 per 1000 person-year). A positive correlation was observed between SUA level and CV risk in the general population, whereas CV risk was consistently high in gout population, regardless of SUA level. A favorable lifestyle was associated with lower CV risk in both patients with gout and participants without gout. In all categories of SUA levels (&lt; 6mg/dL, normal; 6-8.9 mg/dL, high; ≥ 9mg/dL, very high), CV risk was significantly lower in gout patients with a favorable lifestyle than in those with a unfavorable lifestyle. <h3>Conclusion</h3> Patients with gout are at high risk of CVD even with SUA levels in the normal range. Lifestyle modification can be an effective and inexpensive therapeutic strategy to prevent CV events in patients with gout. <h3>References</h3> [1]Khera, A.V., et al., <i>Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease.</i> N Engl J Med, 2016. <b>375</b>(24): p. 2349-2358. [2]Rutten-Jacobs, L.C., et al., <i>Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants.</i> BMJ, 2018. <b>363</b>: p. k4168. [3]Feig, D.I., D.H. Kang, and R.J. Johnson, <i>Uric acid and cardiovascular risk.</i> N Engl J Med, 2008. <b>359</b>(17): p. 1811-21. [4]rosos, G.C., et al., <i>EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome.</i> Ann Rheum Dis, 2022. [5]Zhang, Y., et al., <i>Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: a large population-based longitudinal study.</i> BMC Med, 2022. <b>20</b>(1): p. 138. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS0555 HIGH DOSE INTRAVENOUS ANAKINRA TREATMENT IS SAFE AND EFFECTIVE IN SEVERE AND CRITICAL COVID-19 PATIENTS: A PROPENSITY SCORE MATCHED STUDY IN A SINGLE CENTER
Authors: M. Bektaş, S. Yüce, M. Ay, M. Uyar, M. Önder, M. İ. Kiliç
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In COVID-19 severe disease course such as need of intensive care unit (ICU) as well as development of mortality is mainly due to cytokine storm. <h3>Objectives</h3> In this study, we aimed to evaluate the high dose intravenous anakinra treatment response and outcome in patients with severe and critical COVID-19 compared to standard of care. <h3>Methods</h3> This retrospective observational study was carried out at a tertiary referral center. The study population consisted of two groups as follows; the patients receiving high dose intravenous anakinra (anakinra group) between 01.09.2021 and 01.02.2022 and the patients treated with standard of care (SoC, control group) as historical control group who were hospitalized between 01.07.2021 and 01.09.2021. <h3>Results</h3> After the propensity score 1:1 matching 79 patients in anakinra and 79 patients in SoC matched and included into the analysis. Mean±SD patient age was 67.4±16.7 and 67.1±16.3 years in anakinra and SoC group, respectively (p=0.9). Male gender was 38 (48.7 %) in anakinra and 36 (46.2 %) SoC (p=0.8). Overall, ICU admission was in 14.1 % (n=11) and 30.8 % (n=24) (p=0.013; OR: 6.2), intubation in 12.8 % (n=10) and 16.7 % (n=13) patients (p=0.5), 14.1 % (n=11) and 32.1 % (n=25) patients died in anakinra and control group, respectively (p=0.008; OR: 7.1) <h3>Conclusion</h3> In our study mortality was lower in patients receiving anakinra compared to SoC. Intravenous high dose anakinra is safe and effective treatment in patients with severe and critical COVID-19. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.